In brief

Through single-cell sequencing, researchers created a comprehensive database of skin dendritic cells and found that a new subtype, CD14+ DC3, produces key triggering proteins in psoriasis.

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Digging skin deep for a cause

15 Nov 2022

The identification of a class of inflammatory immune cells offers new opportunities to treat chronic skin conditions.

When American astrophysicist Neil deGrasse Tyson said that “we are, each of us, a little universe”, he was referring to the myriad of atoms, molecules and dynamic chemical reactions that make up the human body. For example, a peek just below the skin, reveals numerous immune cells keenly keeping watch for potentially dangerous invaders.

Sometimes, however, these immune guardians can backfire. T cells, usually activated by antigen-presenting immune cells called dendritic cells (DCs) to produce inflammatory factors in response to invaders, can be overactive and result in chronic inflammatory skin conditions such as eczema and psoriasis.

“Antigen-presenting cells are essential for T cell activation, but their classification and function in skin is not clearly understood,” explained Kenji Kabashima, Senior Principal Investigator at the A*STAR Skin Research Labs (A*SRL), adding that within this vast, unexplored universe lies potential drug targets to calm chronic skin flare-ups.

Kabashima and his team took on the challenge of mapping DCs in healthy and inflamed skin, one cell at a time. First, they collected skin samples from patients with inflammatory skin conditions and classified DCs and other immune cells individually using flow cytometry. They then employed cutting-edge single-cell sequencing technology to decode the RNA signatures in these cells.

The researchers’ efforts culminated in the first-ever comprehensive database of skin DCs, which includes the molecular profiles of healthy cells as well as those involved in inflammatory skin diseases.

“The single-cell universe of DCs is a new classification scheme of antigen-presenting cells based on single-cell-level analysis,” said Satoshi Nakamizo, first author of the study, adding that these new classifications provide a more holistic understanding of connections between dendritic cell function and their roles in chronic disease.

As part of the team’s analysis, the scientists uncovered a novel dendritic cell subtype called CD14+ DC3. These cells produce the immune-activating proteins IL1B and IL23A, both of which are known triggers of the red and scaly patches associated with psoriasis.

Nakamizo said that the study identifies CD14+ DC3s as a new potentially druggable target to treat psoriasis, dermatitis and other inflammatory skin conditions. However, this dataset is just the tip of the iceberg. According to Kabashima, future single-cell sequencing efforts will focus on understanding where DCs lie within the complex skin architecture and how they interact with other skin cells.

“In addition, similar analyses are currently underway for skin diseases other than atopic dermatitis and psoriasis,” concluded Kabashima.

The A*STAR-affiliated researchers contributing to this research are from the A*STAR Skin Research Labs (A*SRL) and Singapore Immunology Network (SIgN).

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Nakamizo, S., Dutertre, C.A., Khalilnezhad, A., Zhang, X.M., Lim, S. et al . Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A in psoriasis, Journal of Experimental Medicine 218:e20202345 (2021) | article

About the Researchers

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Satoshi Nakamizo

Satoshi Nakamizo is currently an assistant professor at Kyoto University in Japan. He obtained his PhD from Kyoto University, Japan in 2015. From 2016 to 2020, he was a Senior Research Fellow at the Institute of Medical Biology and Singapore Immunology Network. Together with Florent Ginhoux and Kenji Kabashima, he worked on the relationship between diet and skin condition and the identification of antigen-presenting cells in inflammatory skin diseases.
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Kenji Kabashima

Senior Principal Investigator

A*STAR Skin Research Labs (A*SRL)
Kenji Kabashima graduated from Kyoto University in 1996 and underwent Medicine and Dermatology training at the United States Naval Hospital in Yokosuka Japan, Kyoto University Hospital and University of Washington Medical Center. His research interests include atopic dermatitis, its pathogenesis and potential treatments. He is also working on gene-targeted fluorescent chemical probes to visualise cells to help understand the mechanisms underpinning skin homeostasis. Previously with the Singapore Immunology Network (SIgN), Kabashima currently serves as a Senior Principal Investigator at the A*STAR Skin Research Labs (A*SRL).
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Florent Ginhoux

Senior Principal Investigator

Singapore Immunology Network
Florent Ginhoux completed his undergraduate studies at the University Pierre et Marie Curie (UPMC), Paris VI. He subsequently obtained a Master’s degree from the Pasteur Institute in 2000 and his PhD from UPMC, Paris VI, in 2004. He is currently a Senior Principal Investigator at A*STAR’s Singapore Immunology Network (SIgN) and an EMBO Young Investigator. His laboratory focuses on the ontogeny and differentiation of macrophages and dendritic cells in both humans and mice. He was listed as a highly cited researcher on Web of Science in 2016, 2017 and 2018.

This article was made for A*STAR Research by Wildtype Media Group